Chordoma is a rare, slow growing, often fatal bone cancer derived from remnants of the embryonic notochord. It occurs mostly in the axial skeleton (skull base, vertebrae, sacrum and coccyx), is more frequent in males than females, and has a median age at diagnosis of 58.5 years, with a wide age range. This typically sporadic tumor is often advanced at presentation, and mortality is high due to local recurrence or distant metastases. The usual treatment is surgery, followed by adjuvant radiation therapy. Chemotherapy has not had a significant treatment role. Reports of a small number of families worldwide with two or more relatives with chordoma support a role for susceptibility genes in chordoma etiology. Recently we determined that duplications of the T gene co-segregated with disease in four multiplex chordoma families. The T gene encodes brachyury, a tissue-specific transcription factor that is expressed in notochord cells and is essential for formation and maintenance of the notochord. Some of the other chordoma families that we studied did not have T-gene duplications; the aggregation of chordomas in these families may result from changes in other susceptibility genes or other types of mutations targeting the T gene. We are continuing gene identification studies of multiplex chordoma families at the NIH Clinical Center under protocol 78-C-0039. We also want to determine whether alterations in any identified chordoma susceptibility genes are associated with sporadic chordoma in the general population.

Objectives:

The major goal of this protocol is to identify sporadic chordoma patients willing to provide germline and tumor DNA for studies to determine the frequency of alterations in chordoma susceptibility genes. Our previous protocols with SEER and Massachusetts General Hospital to identify chordoma patients were limited to residents of specific geographic regions in the U.S. (2 states and 2 metropolitan areas) or to patients with pediatric skull base tumors. This protocol will enroll patients who more broadly represent the age, site and gender distributions of sporadic chordoma in the general U.S. population.

Eligibility:

Eligible patients are males and females in the U.S. with chordoma diagnosed at any age and at any primary site. Because we want to obtain saliva from all participants, eligibility is limited to patients who will be greater than or equal to age 6 years at the time of enrollment.

Design:

The study description and contacting information including an e-mail link to the study contact person will be posted on web sites of two chordoma support groups. We will mail study information to be given to patients to colleagues at major medical centers that treat chordoma.

The components of the study will be carried out in subjects' homes using materials mailed to them. Up to 100 participants will: 1) complete a self-administered Personal and Family Medical History Questionnaire, 2) collect saliva using a saliva collection kit, and 3) provide permission to obtain medical/pathology records, and paraffin blocks or slides on each primary chordoma. Parents will serve as proxies for minor children.

We will recontact patients who report chordoma in at least one blood relative. If we confirm the relative's chordoma diagnosis, we will invite the study subject and selected family members to participate in clinical and gene mapping studies under protocol 78-C-0039. We may also recontact study participants to tell them about any new studies on chordoma etiology. They can decide at that time whether they want to participate in them.

Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):

Primary Outcome Measures:

To determine the frequency of alterations in chordoma susceptibility genes in the general population [ Time Frame: Multiple/ongoing ]

Estimated Enrollment:

400

Study Start Date:

August 29, 2010

Detailed Description:

Background:

Chordoma is a rare, slow growing, often fatal bone cancer derived from notochord remnants. It occurs in the axial skeleton (skull base, vertebrae, sacrum, coccyx), is more frequent in males, and has a median age at diagnosis of 58.5 years, with a wide age range. This typically sporadic tumor is often advanced at presentation, and mortality is high due to local recurrence or distant metastases. The usual treatment is surgery, followed by adjuvant radiation therapy. Chemotherapy has not had a significant treatment role. Reports of a few families with two or more relatives with chordoma support an etiologic role for chordoma susceptibility genes. We determined that T-gene duplications co-segregated with disease in four multiplex chordoma families. The T gene encodes brachyury, a tissue-specific transcription factor expressed in notochord cells that is essential for notochord formation and maintenance. The other chordoma families that we studied did not have T-gene duplications; chordomas in these families may result from changes in other susceptibility genes or other types of T-gene mutations. We are continuing gene identification studies of multiplex chordoma families under NIH protocol 78-C-0039. We also want to determine whether alterations in any identified chordoma susceptibility genes are associated with sporadic chordoma in the general populations.

Objectives:

The major goal of this protocol is to identify sporadic chordoma patients willing to provide germline and tumor DNA for studies to determine the frequency of alterations in chordoma susceptibility genes. Our previous protocols with SEER and Massachusetts General Hospital to identify chordoma patients were limited to residents of specific regions (2 states and 2 metropolitan areas) or to patients with pediatric skull base tumors. This protocol will enroll patients who more broadly represent the age, site and gender distributions of sporadic chordoma in the general population.

Eligibility:

Eligible patients are males and females with chordoma diagnosed at any age and at any primary site. Because we want to obtain saliva from all participants, eligibility is limited to patients who will be greater than or equal to age 6 years at time of enrollment.

Design:

The study description and contact information including an e-mail link to the study contact person will be posted on web sites of two chordoma support groups. We will mail study information to be given to patients to colleagues at major medical centers that treat chordoma.

The components of the study will be carried out in subjects' homes using materials mailed to them. Up to 100 participants will: 1) complete a self-administered Personal and Family Medical Questionnaire, 2) collect saliva using a saliva collection kit, and 3) provide permission to obtain medical/pathology records, and paraffin blocks or slides on each primary chordoma. Parents will serve as proxies for minor children.

We will recontact patients who report chordoma in at least one blood relative. If we confirm the relative's chordoma diagnosis, we will invite the study subject and selected family members to participate in clinical and gene mapping studies under protocol 78-C-0039. We may also recontact study participants to tell them about any new studies on chordoma etiology. They can decide at that time whether they want to participate in them.

Eligibility

Ages Eligible for Study:

6 Years to 100 Years (Child, Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

ELIGIBILITY CRITERIA:

To be eligible subjects must be at least 6 years old at the time of enrollment, be the only person in their family ever diagnosed with chordoma, and reside in the U.S or Canada.

Chordoma in the patients can have been diagnosed at any age and any primary site.

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01200680